CA3219606A1 - Heterodimeric fc domain antibodies - Google Patents

Heterodimeric fc domain antibodies Download PDF

Info

Publication number: CA3219606A1
Authority: CA; Canada
Prior art keywords: domain; antibody; amino acid; antigen binding; seq
Prior art date: 2021-07-22
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Pending

Application number

CA3219606A

Other languages

English (en)

French (fr)

Inventor

Diana DAROWSKI

Anne Freimoser-Grundschober

Christian Klein

Ekkehard Moessner

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

F Hoffmann La Roche AG

Original Assignee

F Hoffmann La Roche AG

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2021-07-22

Filing date

2022-07-20

Publication date

2023-01-26

2022-07-20 Application filed by F Hoffmann La Roche AG filed Critical F Hoffmann La Roche AG

2023-01-26 Publication of CA3219606A1 publication Critical patent/CA3219606A1/en

Status Pending legal-status Critical Current

Links

239000000427 antigen Substances 0.000 claims abstract description 444
230000027455 binding Effects 0.000 claims abstract description 439
108091007433 antigens Proteins 0.000 claims abstract description 438
102000036639 antigens Human genes 0.000 claims abstract description 438
210000001744 T-lymphocyte Anatomy 0.000 claims abstract description 162
150000001413 amino acids Chemical class 0.000 claims abstract description 153
230000035772 mutation Effects 0.000 claims abstract description 105
206010028980 Neoplasm Diseases 0.000 claims abstract description 87
230000009870 specific binding Effects 0.000 claims abstract description 48
210000004027 cell Anatomy 0.000 claims description 227
102000005962 receptors Human genes 0.000 claims description 222
108020003175 receptors Proteins 0.000 claims description 222
230000011664 signaling Effects 0.000 claims description 134
238000000034 method Methods 0.000 claims description 128
108010047041 Complementarity Determining Regions Proteins 0.000 claims description 94
239000012634 fragment Substances 0.000 claims description 93
201000011510 cancer Diseases 0.000 claims description 58
230000004936 stimulating effect Effects 0.000 claims description 57
101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 claims description 53
102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 claims description 53
230000014509 gene expression Effects 0.000 claims description 50
101000851370 Homo sapiens Tumor necrosis factor receptor superfamily member 9 Proteins 0.000 claims description 39
102100036856 Tumor necrosis factor receptor superfamily member 9 Human genes 0.000 claims description 35
230000003834 intracellular effect Effects 0.000 claims description 35
238000012986 modification Methods 0.000 claims description 35
230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 claims description 34
230000004048 modification Effects 0.000 claims description 34
238000011282 treatment Methods 0.000 claims description 31
102100027207 CD27 antigen Human genes 0.000 claims description 29
101000914511 Homo sapiens CD27 antigen Proteins 0.000 claims description 29
101001109501 Homo sapiens NKG2-D type II integral membrane protein Proteins 0.000 claims description 29
101000809875 Homo sapiens TYRO protein tyrosine kinase-binding protein Proteins 0.000 claims description 27
102100022680 NKG2-D type II integral membrane protein Human genes 0.000 claims description 27
239000003814 drug Substances 0.000 claims description 27
101000990188 Homo sapiens Hematopoietic cell signal transducer Proteins 0.000 claims description 26
102100038717 TYRO protein tyrosine kinase-binding protein Human genes 0.000 claims description 25
102100029360 Hematopoietic cell signal transducer Human genes 0.000 claims description 24
238000004519 manufacturing process Methods 0.000 claims description 23
239000008194 pharmaceutical composition Substances 0.000 claims description 23
102000040430 polynucleotide Human genes 0.000 claims description 23
108091033319 polynucleotide Proteins 0.000 claims description 23
239000002157 polynucleotide Substances 0.000 claims description 23
239000012636 effector Substances 0.000 claims description 21
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 18
-1 CD52F1t3 Proteins 0.000 claims description 16
108010087819 Fc receptors Proteins 0.000 claims description 16
102000009109 Fc receptors Human genes 0.000 claims description 16
230000001965 increasing effect Effects 0.000 claims description 14
102100022005 B-lymphocyte antigen CD20 Human genes 0.000 claims description 12
101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 claims description 12
101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 claims description 12
230000001737 promoting effect Effects 0.000 claims description 11
102000007000 Tenascin Human genes 0.000 claims description 10
108010008125 Tenascin Proteins 0.000 claims description 10
108010066687 Epithelial Cell Adhesion Molecule Proteins 0.000 claims description 9
102000018651 Epithelial Cell Adhesion Molecule Human genes 0.000 claims description 9
102100029193 Low affinity immunoglobulin gamma Fc region receptor III-A Human genes 0.000 claims description 9
239000003937 drug carrier Substances 0.000 claims description 9
102100025475 Carcinoembryonic antigen-related cell adhesion molecule 5 Human genes 0.000 claims description 8
102100041003 Glutamate carboxypeptidase 2 Human genes 0.000 claims description 8
101000916489 Homo sapiens Chondroitin sulfate proteoglycan 4 Proteins 0.000 claims description 7
101000892862 Homo sapiens Glutamate carboxypeptidase 2 Proteins 0.000 claims description 7
102100036735 Prostate stem cell antigen Human genes 0.000 claims description 6
238000012258 culturing Methods 0.000 claims description 6
102100038080 B-cell receptor CD22 Human genes 0.000 claims description 5
101000884305 Homo sapiens B-cell receptor CD22 Proteins 0.000 claims description 5
101000934338 Homo sapiens Myeloid cell surface antigen CD33 Proteins 0.000 claims description 5
102100025243 Myeloid cell surface antigen CD33 Human genes 0.000 claims description 5
102000006942 B-Cell Maturation Antigen Human genes 0.000 claims description 4
108010008014 B-Cell Maturation Antigen Proteins 0.000 claims description 4
108010033576 Transferrin Receptors Proteins 0.000 claims description 4
102100031585 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Human genes 0.000 claims description 3
102100024222 B-lymphocyte antigen CD19 Human genes 0.000 claims description 3
101000777636 Homo sapiens ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Proteins 0.000 claims description 3
101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 claims description 3
108700012439 CA9 Proteins 0.000 claims description 2
102100024423 Carbonic anhydrase 9 Human genes 0.000 claims description 2
101001056234 Homo sapiens Sperm mitochondrial-associated cysteine-rich protein Proteins 0.000 claims description 2
BGFTWECWAICPDG-UHFFFAOYSA-N 2-[bis(4-chlorophenyl)methyl]-4-n-[3-[bis(4-chlorophenyl)methyl]-4-(dimethylamino)phenyl]-1-n,1-n-dimethylbenzene-1,4-diamine Chemical compound C1=C(C(C=2C=CC(Cl)=CC=2)C=2C=CC(Cl)=CC=2)C(N(C)C)=CC=C1NC(C=1)=CC=C(N(C)C)C=1C(C=1C=CC(Cl)=CC=1)C1=CC=C(Cl)C=C1 BGFTWECWAICPDG-UHFFFAOYSA-N 0.000 claims 1
101100412446 Caenorhabditis elegans rer-1 gene Proteins 0.000 claims 1
102100035139 Folate receptor alpha Human genes 0.000 claims 1
102000006354 HLA-DR Antigens Human genes 0.000 claims 1
108010058597 HLA-DR Antigens Proteins 0.000 claims 1
101001023230 Homo sapiens Folate receptor alpha Proteins 0.000 claims 1
101000576802 Homo sapiens Mesothelin Proteins 0.000 claims 1
101000829725 Homo sapiens Phospholipid hydroperoxide glutathione peroxidase Proteins 0.000 claims 1
101001136592 Homo sapiens Prostate stem cell antigen Proteins 0.000 claims 1
102100025096 Mesothelin Human genes 0.000 claims 1
101150004182 RER2 gene Proteins 0.000 claims 1
102100026503 Sperm mitochondrial-associated cysteine-rich protein Human genes 0.000 claims 1
102000007238 Transferrin Receptors Human genes 0.000 claims 1
229920001481 poly(stearyl methacrylate) Polymers 0.000 claims 1
230000008685 targeting Effects 0.000 abstract description 7
125000003275 alpha amino acid group Chemical group 0.000 description 182
235000001014 amino acid Nutrition 0.000 description 151
108090000765 processed proteins & peptides Proteins 0.000 description 149
229940024606 amino acid Drugs 0.000 description 124
150000007523 nucleic acids Chemical class 0.000 description 87
102000039446 nucleic acids Human genes 0.000 description 82
108020004707 nucleic acids Proteins 0.000 description 82
102000004196 processed proteins & peptides Human genes 0.000 description 81
229920001184 polypeptide Polymers 0.000 description 79
108090000623 proteins and genes Proteins 0.000 description 68
239000013598 vector Substances 0.000 description 67
238000004873 anchoring Methods 0.000 description 60
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 58
238000006467 substitution reaction Methods 0.000 description 53
235000018102 proteins Nutrition 0.000 description 40
102000004169 proteins and genes Human genes 0.000 description 40
108060003951 Immunoglobulin Proteins 0.000 description 28
102000018358 immunoglobulin Human genes 0.000 description 28
238000003556 assay Methods 0.000 description 25
230000000694 effects Effects 0.000 description 25
230000006870 function Effects 0.000 description 25
230000004913 activation Effects 0.000 description 22
125000000539 amino acid group Chemical group 0.000 description 22
241000699666 Mus <mouse, genus> Species 0.000 description 21
108091028043 Nucleic acid sequence Proteins 0.000 description 21
238000013459 approach Methods 0.000 description 21
150000002482 oligosaccharides Chemical class 0.000 description 21
241001529936 Murinae Species 0.000 description 20
239000000203 mixture Substances 0.000 description 20
210000004899 c-terminal region Anatomy 0.000 description 19
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 19
125000003729 nucleotide group Chemical group 0.000 description 19
210000004881 tumor cell Anatomy 0.000 description 19
239000013604 expression vector Substances 0.000 description 18
230000001976 improved effect Effects 0.000 description 18
239000002773 nucleotide Substances 0.000 description 18
229920001542 oligosaccharide Polymers 0.000 description 18
102000008394 Immunoglobulin Fragments Human genes 0.000 description 16
108010021625 Immunoglobulin Fragments Proteins 0.000 description 16
238000005516 engineering process Methods 0.000 description 15
238000003780 insertion Methods 0.000 description 15
230000037431 insertion Effects 0.000 description 15
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 14
102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 0.000 description 14
210000004369 blood Anatomy 0.000 description 14
239000008280 blood Substances 0.000 description 14
201000010099 disease Diseases 0.000 description 14
230000003993 interaction Effects 0.000 description 14
102000053602 DNA Human genes 0.000 description 13
108020004414 DNA Proteins 0.000 description 13
238000001727 in vivo Methods 0.000 description 13
108020004999 messenger RNA Proteins 0.000 description 13
230000001225 therapeutic effect Effects 0.000 description 13
108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 12
102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 12
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 12
238000005734 heterodimerization reaction Methods 0.000 description 12
230000002829 reductive effect Effects 0.000 description 12
102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 description 11
108050005493 CD3 protein, epsilon/gamma/delta subunit Proteins 0.000 description 11
108010019670 Chimeric Antigen Receptors Proteins 0.000 description 11
108020001507 fusion proteins Proteins 0.000 description 11
102000037865 fusion proteins Human genes 0.000 description 11
102000004127 Cytokines Human genes 0.000 description 10
108090000695 Cytokines Proteins 0.000 description 10
KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 10
230000004075 alteration Effects 0.000 description 10
230000000295 complement effect Effects 0.000 description 10
238000012217 deletion Methods 0.000 description 10
230000037430 deletion Effects 0.000 description 10
210000002865 immune cell Anatomy 0.000 description 10
230000001105 regulatory effect Effects 0.000 description 10
210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 9
102100026120 IgG receptor FcRn large subunit p51 Human genes 0.000 description 9
108010002350 Interleukin-2 Proteins 0.000 description 9
102000000588 Interleukin-2 Human genes 0.000 description 9
230000004540 complement-dependent cytotoxicity Effects 0.000 description 9
230000004927 fusion Effects 0.000 description 9
229940124597 therapeutic agent Drugs 0.000 description 9
108020004635 Complementary DNA Proteins 0.000 description 8
239000004471 Glycine Substances 0.000 description 8
101710177940 IgG receptor FcRn large subunit p51 Proteins 0.000 description 8
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 8
230000003213 activating effect Effects 0.000 description 8
125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 8
230000013595 glycosylation Effects 0.000 description 8
238000006206 glycosylation reaction Methods 0.000 description 8
239000012528 membrane Substances 0.000 description 8
238000012552 review Methods 0.000 description 8
229920002477 rna polymer Polymers 0.000 description 8
238000002560 therapeutic procedure Methods 0.000 description 8
238000010361 transduction Methods 0.000 description 8
230000026683 transduction Effects 0.000 description 8
108010022366 Carcinoembryonic Antigen Proteins 0.000 description 7
238000002965 ELISA Methods 0.000 description 7
102000010451 Folate receptor alpha Human genes 0.000 description 7
108050001931 Folate receptor alpha Proteins 0.000 description 7
CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 7
102000003735 Mesothelin Human genes 0.000 description 7
108090000015 Mesothelin Proteins 0.000 description 7
241001465754 Metazoa Species 0.000 description 7
230000000890 antigenic effect Effects 0.000 description 7
230000004071 biological effect Effects 0.000 description 7
230000015572 biosynthetic process Effects 0.000 description 7
238000010804 cDNA synthesis Methods 0.000 description 7
239000003795 chemical substances by application Substances 0.000 description 7
239000002299 complementary DNA Substances 0.000 description 7
230000009089 cytolysis Effects 0.000 description 7
229940079593 drug Drugs 0.000 description 7
230000003511 endothelial effect Effects 0.000 description 7
210000004408 hybridoma Anatomy 0.000 description 7
229940072221 immunoglobulins Drugs 0.000 description 7
238000000338 in vitro Methods 0.000 description 7
230000001404 mediated effect Effects 0.000 description 7
210000001616 monocyte Anatomy 0.000 description 7
230000001177 retroviral effect Effects 0.000 description 7
NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 6
241000894006 Bacteria Species 0.000 description 6
206010006187 Breast cancer Diseases 0.000 description 6
102100028757 Chondroitin sulfate proteoglycan 4 Human genes 0.000 description 6
241000196324 Embryophyta Species 0.000 description 6
WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 6
XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 6
DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 6
ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 6
LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical group CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 6
COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 6
AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 6
239000004472 Lysine Substances 0.000 description 6
239000002202 Polyethylene glycol Substances 0.000 description 6
208000000453 Skin Neoplasms Diseases 0.000 description 6
KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 6
125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 6
238000010367 cloning Methods 0.000 description 6
230000001419 dependent effect Effects 0.000 description 6
238000010494 dissociation reaction Methods 0.000 description 6
230000005593 dissociations Effects 0.000 description 6
230000036541 health Effects 0.000 description 6
230000001900 immune effect Effects 0.000 description 6
230000001939 inductive effect Effects 0.000 description 6
239000002609 medium Substances 0.000 description 6
238000002823 phage display Methods 0.000 description 6
229920001223 polyethylene glycol Polymers 0.000 description 6
229920000642 polymer Polymers 0.000 description 6
239000000047 product Substances 0.000 description 6
230000035755 proliferation Effects 0.000 description 6
238000011002 quantification Methods 0.000 description 6
238000012216 screening Methods 0.000 description 6
201000000849 skin cancer Diseases 0.000 description 6
239000000126 substance Substances 0.000 description 6
238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 6
MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 5
208000026310 Breast neoplasm Diseases 0.000 description 5
108091026890 Coding region Proteins 0.000 description 5
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 5
206010017993 Gastrointestinal neoplasms Diseases 0.000 description 5
206010058467 Lung neoplasm malignant Diseases 0.000 description 5
208000003445 Mouth Neoplasms Diseases 0.000 description 5
108010008707 Mucin-1 Proteins 0.000 description 5
102100034256 Mucin-1 Human genes 0.000 description 5
206010033128 Ovarian cancer Diseases 0.000 description 5
206010061535 Ovarian neoplasm Diseases 0.000 description 5
206010061902 Pancreatic neoplasm Diseases 0.000 description 5
108091005804 Peptidases Proteins 0.000 description 5
101710120463 Prostate stem cell antigen Proteins 0.000 description 5
239000004365 Protease Substances 0.000 description 5
108010076504 Protein Sorting Signals Proteins 0.000 description 5
108010003723 Single-Domain Antibodies Proteins 0.000 description 5
239000004098 Tetracycline Substances 0.000 description 5
239000004480 active ingredient Substances 0.000 description 5
230000002411 adverse Effects 0.000 description 5
235000018417 cysteine Nutrition 0.000 description 5
XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 5
230000001472 cytotoxic effect Effects 0.000 description 5
208000035475 disorder Diseases 0.000 description 5
230000007783 downstream signaling Effects 0.000 description 5
239000003623 enhancer Substances 0.000 description 5
210000003527 eukaryotic cell Anatomy 0.000 description 5
230000002068 genetic effect Effects 0.000 description 5
125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 5
238000011534 incubation Methods 0.000 description 5
208000012987 lip and oral cavity carcinoma Diseases 0.000 description 5
239000002502 liposome Substances 0.000 description 5
201000005202 lung cancer Diseases 0.000 description 5
208000020816 lung neoplasm Diseases 0.000 description 5
208000015486 malignant pancreatic neoplasm Diseases 0.000 description 5
210000000822 natural killer cell Anatomy 0.000 description 5
201000002528 pancreatic cancer Diseases 0.000 description 5
208000008443 pancreatic carcinoma Diseases 0.000 description 5
239000002953 phosphate buffered saline Substances 0.000 description 5
239000013612 plasmid Substances 0.000 description 5
238000003752 polymerase chain reaction Methods 0.000 description 5
238000002360 preparation method Methods 0.000 description 5
239000000243 solution Substances 0.000 description 5
229960002180 tetracycline Drugs 0.000 description 5
229930101283 tetracycline Natural products 0.000 description 5
235000019364 tetracycline Nutrition 0.000 description 5
150000003522 tetracyclines Chemical class 0.000 description 5
238000013518 transcription Methods 0.000 description 5
230000035897 transcription Effects 0.000 description 5
230000002463 transducing effect Effects 0.000 description 5
238000001890 transfection Methods 0.000 description 5
241000282693 Cercopithecidae Species 0.000 description 4
WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 4
SHZGCJCMOBCMKK-DHVFOXMCSA-N L-fucopyranose Chemical compound C[C@@H]1OC(O)[C@@H](O)[C@H](O)[C@@H]1O SHZGCJCMOBCMKK-DHVFOXMCSA-N 0.000 description 4
ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 4
OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 4
241000124008 Mammalia Species 0.000 description 4
OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 description 4
MBLBDJOUHNCFQT-LXGUWJNJSA-N N-acetylglucosamine Natural products CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-LXGUWJNJSA-N 0.000 description 4
102000035195 Peptidases Human genes 0.000 description 4
241000700159 Rattus Species 0.000 description 4
240000004808 Saccharomyces cerevisiae Species 0.000 description 4
230000006044 T cell activation Effects 0.000 description 4
AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 4
239000004473 Threonine Substances 0.000 description 4
108091023040 Transcription factor Proteins 0.000 description 4
101150063416 add gene Proteins 0.000 description 4
230000000735 allogeneic effect Effects 0.000 description 4
239000011230 binding agent Substances 0.000 description 4
239000000872 buffer Substances 0.000 description 4
230000001413 cellular effect Effects 0.000 description 4
231100000433 cytotoxic Toxicity 0.000 description 4
230000007423 decrease Effects 0.000 description 4
210000004443 dendritic cell Anatomy 0.000 description 4
108010048367 enhanced green fluorescent protein Proteins 0.000 description 4
238000000684 flow cytometry Methods 0.000 description 4
102000004632 fms-Like Tyrosine Kinase 3 Human genes 0.000 description 4
108010003374 fms-Like Tyrosine Kinase 3 Proteins 0.000 description 4
238000010353 genetic engineering Methods 0.000 description 4
239000005090 green fluorescent protein Substances 0.000 description 4
230000028993 immune response Effects 0.000 description 4
238000002347 injection Methods 0.000 description 4
239000007924 injection Substances 0.000 description 4
210000003292 kidney cell Anatomy 0.000 description 4
230000002101 lytic effect Effects 0.000 description 4
210000002540 macrophage Anatomy 0.000 description 4
125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 4
239000003094 microcapsule Substances 0.000 description 4
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
210000001236 prokaryotic cell Anatomy 0.000 description 4
238000000159 protein binding assay Methods 0.000 description 4
230000005180 public health Effects 0.000 description 4
238000000746 purification Methods 0.000 description 4
230000009467 reduction Effects 0.000 description 4
230000004044 response Effects 0.000 description 4
239000000523 sample Substances 0.000 description 4
230000007781 signaling event Effects 0.000 description 4
238000002741 site-directed mutagenesis Methods 0.000 description 4
238000003786 synthesis reaction Methods 0.000 description 4
210000001519 tissue Anatomy 0.000 description 4
230000009261 transgenic effect Effects 0.000 description 4
239000013603 viral vector Substances 0.000 description 4
239000004475 Arginine Substances 0.000 description 3
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
102000004190 Enzymes Human genes 0.000 description 3
108090000790 Enzymes Proteins 0.000 description 3
241000588724 Escherichia coli Species 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
102000003886 Glycoproteins Human genes 0.000 description 3
108090000288 Glycoproteins Proteins 0.000 description 3
241000238631 Hexapoda Species 0.000 description 3
241000282412 Homo Species 0.000 description 3
101100166600 Homo sapiens CD28 gene Proteins 0.000 description 3
101500025419 Homo sapiens Epidermal growth factor Proteins 0.000 description 3
101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 description 3
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 3
HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 3
QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 3
OVRNDRQMDRJTHS-RTRLPJTCSA-N N-acetyl-D-glucosamine Chemical compound CC(=O)N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-RTRLPJTCSA-N 0.000 description 3
108091007491 NSP3 Papain-like protease domains Proteins 0.000 description 3
229920001213 Polysorbate 20 Polymers 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 3
102100037906 T-cell surface glycoprotein CD3 zeta chain Human genes 0.000 description 3
102000040945 Transcription factor Human genes 0.000 description 3
102100026144 Transferrin receptor protein 1 Human genes 0.000 description 3
QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 3
241000251539 Vertebrata <Metazoa> Species 0.000 description 3
241000700605 Viruses Species 0.000 description 3
230000009824 affinity maturation Effects 0.000 description 3
235000004279 alanine Nutrition 0.000 description 3
230000000259 anti-tumor effect Effects 0.000 description 3
210000000612 antigen-presenting cell Anatomy 0.000 description 3
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 3
235000003704 aspartic acid Nutrition 0.000 description 3
230000008901 benefit Effects 0.000 description 3
OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 3
230000030833 cell death Effects 0.000 description 3
238000002659 cell therapy Methods 0.000 description 3
210000004978 chinese hamster ovary cell Anatomy 0.000 description 3
238000003776 cleavage reaction Methods 0.000 description 3
238000002648 combination therapy Methods 0.000 description 3
150000001875 compounds Chemical class 0.000 description 3
238000004590 computer program Methods 0.000 description 3
229920001577 copolymer Polymers 0.000 description 3
206010052015 cytokine release syndrome Diseases 0.000 description 3
238000002784 cytotoxicity assay Methods 0.000 description 3
231100000263 cytotoxicity test Toxicity 0.000 description 3
238000001212 derivatisation Methods 0.000 description 3
238000004520 electroporation Methods 0.000 description 3
229940088598 enzyme Drugs 0.000 description 3
230000002349 favourable effect Effects 0.000 description 3
210000002950 fibroblast Anatomy 0.000 description 3
238000001943 fluorescence-activated cell sorting Methods 0.000 description 3
238000009472 formulation Methods 0.000 description 3
230000033581 fucosylation Effects 0.000 description 3
238000001415 gene therapy Methods 0.000 description 3
235000013922 glutamic acid Nutrition 0.000 description 3
239000004220 glutamic acid Substances 0.000 description 3
IKAIKUBBJHFNBZ-UHFFFAOYSA-N glycyl-lysine Chemical group NCCCCC(C(O)=O)NC(=O)CN IKAIKUBBJHFNBZ-UHFFFAOYSA-N 0.000 description 3
HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 3
239000000710 homodimer Substances 0.000 description 3
102000050327 human TNFRSF9 Human genes 0.000 description 3
229940116978 human epidermal growth factor Drugs 0.000 description 3
230000002163 immunogen Effects 0.000 description 3
230000005847 immunogenicity Effects 0.000 description 3
238000001802 infusion Methods 0.000 description 3
230000000977 initiatory effect Effects 0.000 description 3
230000004068 intracellular signaling Effects 0.000 description 3
210000000265 leukocyte Anatomy 0.000 description 3
210000004962 mammalian cell Anatomy 0.000 description 3
239000003550 marker Substances 0.000 description 3
239000000463 material Substances 0.000 description 3
238000005259 measurement Methods 0.000 description 3
GVUGOAYIVIDWIO-UFWWTJHBSA-N nepidermin Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CS)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C(C)C)C(C)C)C1=CC=C(O)C=C1 GVUGOAYIVIDWIO-UFWWTJHBSA-N 0.000 description 3
210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 3
239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 3
235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 3
238000010188 recombinant method Methods 0.000 description 3
238000011160 research Methods 0.000 description 3
230000007017 scission Effects 0.000 description 3
125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 3
210000002966 serum Anatomy 0.000 description 3
125000006850 spacer group Chemical group 0.000 description 3
230000006641 stabilisation Effects 0.000 description 3
238000011105 stabilization Methods 0.000 description 3
235000000346 sugar Nutrition 0.000 description 3
230000001988 toxicity Effects 0.000 description 3
231100000419 toxicity Toxicity 0.000 description 3
230000002103 transcriptional effect Effects 0.000 description 3
238000012546 transfer Methods 0.000 description 3
238000013519 translation Methods 0.000 description 3
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
UKAUYVFTDYCKQA-UHFFFAOYSA-N -2-Amino-4-hydroxybutanoic acid Natural products OC(=O)C(N)CCO UKAUYVFTDYCKQA-UHFFFAOYSA-N 0.000 description 2
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
102100026445 A-kinase anchor protein 17A Human genes 0.000 description 2
241001136782 Alca Species 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 2
125000001433 C-terminal amino-acid group Chemical group 0.000 description 2
102100027209 CD2-associated protein Human genes 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
201000009030 Carcinoma Diseases 0.000 description 2
241000699800 Cricetinae Species 0.000 description 2
241000699802 Cricetulus griseus Species 0.000 description 2
SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 2
229920002307 Dextran Polymers 0.000 description 2
102000001301 EGF receptor Human genes 0.000 description 2
241000206602 Eukaryota Species 0.000 description 2
102000010834 Extracellular Matrix Proteins Human genes 0.000 description 2
108010037362 Extracellular Matrix Proteins Proteins 0.000 description 2
PNNNRSAQSRJVSB-SLPGGIOYSA-N Fucose Natural products C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C=O PNNNRSAQSRJVSB-SLPGGIOYSA-N 0.000 description 2
241000233866 Fungi Species 0.000 description 2
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
101000718019 Homo sapiens A-kinase anchor protein 17A Proteins 0.000 description 2
101001042104 Homo sapiens Inducible T-cell costimulator Proteins 0.000 description 2
PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 2
102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 2
108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 2
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
108010065805 Interleukin-12 Proteins 0.000 description 2
102000013462 Interleukin-12 Human genes 0.000 description 2
102000003812 Interleukin-15 Human genes 0.000 description 2
108090000172 Interleukin-15 Proteins 0.000 description 2
108010002586 Interleukin-7 Proteins 0.000 description 2
102000000704 Interleukin-7 Human genes 0.000 description 2
UKAUYVFTDYCKQA-VKHMYHEASA-N L-homoserine Chemical group OC(=O)[C@@H](N)CCO UKAUYVFTDYCKQA-VKHMYHEASA-N 0.000 description 2
FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical group CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
108700018351 Major Histocompatibility Complex Proteins 0.000 description 2
241000699670 Mus sp. Species 0.000 description 2
102000052812 Ornithine decarboxylases Human genes 0.000 description 2
108700005126 Ornithine decarboxylases Proteins 0.000 description 2
241000283973 Oryctolagus cuniculus Species 0.000 description 2
108091093037 Peptide nucleic acid Proteins 0.000 description 2
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Natural products OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
206010035226 Plasma cell myeloma Diseases 0.000 description 2
239000004372 Polyvinyl alcohol Substances 0.000 description 2
241000288906 Primates Species 0.000 description 2
NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 2
102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 2
108020004511 Recombinant DNA Proteins 0.000 description 2
241000283984 Rodentia Species 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
108091008874 T cell receptors Proteins 0.000 description 2
102000016266 T-Cell Antigen Receptors Human genes 0.000 description 2
101710156660 T-cell surface glycoprotein CD3 zeta chain Proteins 0.000 description 2
108700012920 TNF Proteins 0.000 description 2
102100027212 Tumor-associated calcium signal transducer 2 Human genes 0.000 description 2
ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 2
208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 2
239000012082 adaptor molecule Substances 0.000 description 2
238000012867 alanine scanning Methods 0.000 description 2
HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 2
WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 2
235000009582 asparagine Nutrition 0.000 description 2
229960001230 asparagine Drugs 0.000 description 2
210000003719 b-lymphocyte Anatomy 0.000 description 2
239000008228 bacteriostatic water for injection Substances 0.000 description 2
230000009286 beneficial effect Effects 0.000 description 2
239000001506 calcium phosphate Substances 0.000 description 2
229910000389 calcium phosphate Inorganic materials 0.000 description 2
235000011010 calcium phosphates Nutrition 0.000 description 2
150000001720 carbohydrates Chemical class 0.000 description 2
235000014633 carbohydrates Nutrition 0.000 description 2
229910052799 carbon Inorganic materials 0.000 description 2
YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical compound OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 description 2
238000004113 cell culture Methods 0.000 description 2
210000000170 cell membrane Anatomy 0.000 description 2
201000010881 cervical cancer Diseases 0.000 description 2
230000002759 chromosomal effect Effects 0.000 description 2
210000000349 chromosome Anatomy 0.000 description 2
230000004186 co-expression Effects 0.000 description 2
238000004132 cross linking Methods 0.000 description 2
OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
230000003247 decreasing effect Effects 0.000 description 2
238000001514 detection method Methods 0.000 description 2
230000029087 digestion Effects 0.000 description 2
239000000539 dimer Substances 0.000 description 2
238000006471 dimerization reaction Methods 0.000 description 2
230000003292 diminished effect Effects 0.000 description 2
PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 2
230000003828 downregulation Effects 0.000 description 2
230000009977 dual effect Effects 0.000 description 2
VLCYCQAOQCDTCN-UHFFFAOYSA-N eflornithine Chemical compound NCCCC(N)(C(F)F)C(O)=O VLCYCQAOQCDTCN-UHFFFAOYSA-N 0.000 description 2
210000002744 extracellular matrix Anatomy 0.000 description 2
238000001476 gene delivery Methods 0.000 description 2
208000005017 glioblastoma Diseases 0.000 description 2
UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
229920001519 homopolymer Polymers 0.000 description 2
102000057266 human FCGR3A Human genes 0.000 description 2
102000053803 human HCST Human genes 0.000 description 2
102000043396 human ICOS Human genes 0.000 description 2
102000044042 human KLRK1 Human genes 0.000 description 2
102000045892 human TYROBP Human genes 0.000 description 2
229960002591 hydroxyproline Drugs 0.000 description 2
210000000987 immune system Anatomy 0.000 description 2
230000003053 immunization Effects 0.000 description 2
229940127121 immunoconjugate Drugs 0.000 description 2
230000016784 immunoglobulin production Effects 0.000 description 2
210000000428 immunological synapse Anatomy 0.000 description 2
230000006872 improvement Effects 0.000 description 2
238000000099 in vitro assay Methods 0.000 description 2
239000004615 ingredient Substances 0.000 description 2
229940117681 interleukin-12 Drugs 0.000 description 2
229940100994 interleukin-7 Drugs 0.000 description 2
238000001990 intravenous administration Methods 0.000 description 2
238000001155 isoelectric focusing Methods 0.000 description 2
210000003734 kidney Anatomy 0.000 description 2
230000002147 killing effect Effects 0.000 description 2
238000002843 lactate dehydrogenase assay Methods 0.000 description 2
230000000670 limiting effect Effects 0.000 description 2
210000005229 liver cell Anatomy 0.000 description 2
230000007774 longterm Effects 0.000 description 2
210000004698 lymphocyte Anatomy 0.000 description 2
125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 2
RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 description 2
230000035800 maturation Effects 0.000 description 2
230000007246 mechanism Effects 0.000 description 2
201000001441 melanoma Diseases 0.000 description 2
229910052751 metal Inorganic materials 0.000 description 2
239000002184 metal Chemical class 0.000 description 2
MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 2
229930182817 methionine Chemical group 0.000 description 2
238000002703 mutagenesis Methods 0.000 description 2
231100000350 mutagenesis Toxicity 0.000 description 2
201000000050 myeloid neoplasm Diseases 0.000 description 2
230000007935 neutral effect Effects 0.000 description 2
231100000252 nontoxic Toxicity 0.000 description 2
230000003000 nontoxic effect Effects 0.000 description 2
230000009437 off-target effect Effects 0.000 description 2
210000001672 ovary Anatomy 0.000 description 2
AQIXEPGDORPWBJ-UHFFFAOYSA-N pentan-3-ol Chemical compound CCC(O)CC AQIXEPGDORPWBJ-UHFFFAOYSA-N 0.000 description 2
238000010647 peptide synthesis reaction Methods 0.000 description 2
230000002688 persistence Effects 0.000 description 2
125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 2
229940068977 polysorbate 20 Drugs 0.000 description 2
229920002451 polyvinyl alcohol Polymers 0.000 description 2
239000001267 polyvinylpyrrolidone Substances 0.000 description 2
229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
230000004481 post-translational protein modification Effects 0.000 description 2
239000002243 precursor Substances 0.000 description 2
239000003755 preservative agent Substances 0.000 description 2
230000002265 prevention Effects 0.000 description 2
230000002062 proliferating effect Effects 0.000 description 2
125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
230000000069 prophylactic effect Effects 0.000 description 2
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
230000002285 radioactive effect Effects 0.000 description 2
238000003259 recombinant expression Methods 0.000 description 2
GHMLBKRAJCXXBS-UHFFFAOYSA-N resorcinol Chemical compound OC1=CC=CC(O)=C1 GHMLBKRAJCXXBS-UHFFFAOYSA-N 0.000 description 2
230000000717 retained effect Effects 0.000 description 2
238000002702 ribosome display Methods 0.000 description 2
230000028327 secretion Effects 0.000 description 2
238000013207 serial dilution Methods 0.000 description 2
241000894007 species Species 0.000 description 2
150000008163 sugars Chemical class 0.000 description 2
230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 2
230000004083 survival effect Effects 0.000 description 2
208000024891 symptom Diseases 0.000 description 2
125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 2
RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 2
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
210000003171 tumor-infiltrating lymphocyte Anatomy 0.000 description 2
OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 2
241001515965 unidentified phage Species 0.000 description 2
229920003169 water-soluble polymer Polymers 0.000 description 2
HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
CXNPLSGKWMLZPZ-GIFSMMMISA-N (2r,3r,6s)-3-[[(3s)-3-amino-5-[carbamimidoyl(methyl)amino]pentanoyl]amino]-6-(4-amino-2-oxopyrimidin-1-yl)-3,6-dihydro-2h-pyran-2-carboxylic acid Chemical compound O1[C@@H](C(O)=O)[C@H](NC(=O)C[C@@H](N)CCN(C)C(N)=N)C=C[C@H]1N1C(=O)N=C(N)C=C1 CXNPLSGKWMLZPZ-GIFSMMMISA-N 0.000 description 1
ZMTAPBHUSYTHBY-PMERELPUSA-N (2s)-5-amino-2-[[4-[(2-amino-4-oxo-1h-pteridin-6-yl)methylamino]benzoyl]-[2-[(3',6'-dihydroxy-3-oxospiro[2-benzofuran-1,9'-xanthene]-5-yl)carbamothioylamino]ethyl]amino]-5-oxopentanoic acid Chemical compound N1C(N)=NC(=O)C2=NC(CNC3=CC=C(C=C3)C(=O)N(CCNC(=S)NC=3C=C4C(C5(C6=CC=C(O)C=C6OC6=CC(O)=CC=C65)OC4=O)=CC=3)[C@@H](CCC(=O)N)C(O)=O)=CN=C21 ZMTAPBHUSYTHBY-PMERELPUSA-N 0.000 description 1
WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 1
ASJSAQIRZKANQN-UHFFFAOYSA-N 2-deoxypentose Chemical compound OCC(O)C(O)CC=O ASJSAQIRZKANQN-UHFFFAOYSA-N 0.000 description 1
BRMWTNUJHUMWMS-UHFFFAOYSA-N 3-Methylhistidine Natural products CN1C=NC(CC(N)C(O)=O)=C1 BRMWTNUJHUMWMS-UHFFFAOYSA-N 0.000 description 1
229940117976 5-hydroxylysine Drugs 0.000 description 1
KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
101150026450 Act5C gene Proteins 0.000 description 1
208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 1
229930024421 Adenine Natural products 0.000 description 1
GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
WQVFQXXBNHHPLX-ZKWXMUAHSA-N Ala-Ala-His Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](Cc1cnc[nH]1)C(O)=O WQVFQXXBNHHPLX-ZKWXMUAHSA-N 0.000 description 1
YYSWCHMLFJLLBJ-ZLUOBGJFSA-N Ala-Ala-Ser Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O YYSWCHMLFJLLBJ-ZLUOBGJFSA-N 0.000 description 1
YYAVDNKUWLAFCV-ACZMJKKPSA-N Ala-Ser-Gln Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(O)=O YYAVDNKUWLAFCV-ACZMJKKPSA-N 0.000 description 1
108010088751 Albumins Proteins 0.000 description 1
102000009027 Albumins Human genes 0.000 description 1
102000007698 Alcohol dehydrogenase Human genes 0.000 description 1
108010021809 Alcohol dehydrogenase Proteins 0.000 description 1
102100021266 Alpha-(1,6)-fucosyltransferase Human genes 0.000 description 1
101100067974 Arabidopsis thaliana POP2 gene Proteins 0.000 description 1
PTVGLOCPAVYPFG-CIUDSAMLSA-N Arg-Gln-Asp Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O PTVGLOCPAVYPFG-CIUDSAMLSA-N 0.000 description 1
PTNFNTOBUDWHNZ-GUBZILKMSA-N Asn-Arg-Met Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(O)=O PTNFNTOBUDWHNZ-GUBZILKMSA-N 0.000 description 1
MECFLTFREHAZLH-ACZMJKKPSA-N Asn-Glu-Cys Chemical compound C(CC(=O)O)[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC(=O)N)N MECFLTFREHAZLH-ACZMJKKPSA-N 0.000 description 1
KHCNTVRVAYCPQE-CIUDSAMLSA-N Asn-Lys-Asn Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(O)=O KHCNTVRVAYCPQE-CIUDSAMLSA-N 0.000 description 1
241001465318 Aspergillus terreus Species 0.000 description 1
108091008875 B cell receptors Proteins 0.000 description 1
208000003950 B-cell lymphoma Diseases 0.000 description 1
230000003844 B-cell-activation Effects 0.000 description 1
102000011185 B-lymphocyte antigen CD20 Human genes 0.000 description 1
108050001413 B-lymphocyte antigen CD20 Proteins 0.000 description 1
241000283690 Bos taurus Species 0.000 description 1
108091003079 Bovine Serum Albumin Proteins 0.000 description 1
241000701822 Bovine papillomavirus Species 0.000 description 1
102100021943 C-C motif chemokine 2 Human genes 0.000 description 1
101710155857 C-C motif chemokine 2 Proteins 0.000 description 1
102000007269 CA-125 Antigen Human genes 0.000 description 1
108010008629 CA-125 Antigen Proteins 0.000 description 1
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
241000282465 Canis Species 0.000 description 1
241000282472 Canis lupus familiaris Species 0.000 description 1
229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
108010078791 Carrier Proteins Proteins 0.000 description 1
108010076667 Caspases Proteins 0.000 description 1
102000011727 Caspases Human genes 0.000 description 1
102000000844 Cell Surface Receptors Human genes 0.000 description 1
108010001857 Cell Surface Receptors Proteins 0.000 description 1
102100034231 Cell surface A33 antigen Human genes 0.000 description 1
206010008342 Cervix carcinoma Diseases 0.000 description 1
108091007741 Chimeric antigen receptor T cells Proteins 0.000 description 1
241000282552 Chlorocebus aethiops Species 0.000 description 1
102000011413 Chondroitinases and Chondroitin Lyases Human genes 0.000 description 1
108010023736 Chondroitinases and Chondroitin Lyases Proteins 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
108020004705 Codon Proteins 0.000 description 1
206010009944 Colon cancer Diseases 0.000 description 1
108091035707 Consensus sequence Proteins 0.000 description 1
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
101150074155 DHFR gene Proteins 0.000 description 1
241000702421 Dependoparvovirus Species 0.000 description 1
239000004375 Dextrin Substances 0.000 description 1
229920001353 Dextrin Polymers 0.000 description 1
108010016626 Dipeptides Proteins 0.000 description 1
206010061818 Disease progression Diseases 0.000 description 1
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
108060006698 EGF receptor Proteins 0.000 description 1
102100030801 Elongation factor 1-alpha 1 Human genes 0.000 description 1
108010059378 Endopeptidases Proteins 0.000 description 1
102000005593 Endopeptidases Human genes 0.000 description 1
YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 1
241000283086 Equidae Species 0.000 description 1
208000000461 Esophageal Neoplasms Diseases 0.000 description 1
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
229910052693 Europium Inorganic materials 0.000 description 1
108010091443 Exopeptidases Proteins 0.000 description 1
102000018389 Exopeptidases Human genes 0.000 description 1
241000282326 Felis catus Species 0.000 description 1
101150094690 GAL1 gene Proteins 0.000 description 1
LQEBEXMHBLQMDB-UHFFFAOYSA-N GDP-L-fucose Natural products OC1C(O)C(O)C(C)OC1OP(O)(=O)OP(O)(=O)OCC1C(O)C(O)C(N2C3=C(C(N=C(N)N3)=O)N=C2)O1 LQEBEXMHBLQMDB-UHFFFAOYSA-N 0.000 description 1
LQEBEXMHBLQMDB-JGQUBWHWSA-N GDP-beta-L-fucose Chemical compound O[C@H]1[C@H](O)[C@H](O)[C@H](C)O[C@@H]1OP(O)(=O)OP(O)(=O)OC[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C3=C(C(NC(N)=N3)=O)N=C2)O1 LQEBEXMHBLQMDB-JGQUBWHWSA-N 0.000 description 1
102100028501 Galanin peptides Human genes 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
206010018338 Glioma Diseases 0.000 description 1
WQWMZOIPXWSZNE-WDSKDSINSA-N Gln-Asp-Gly Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(O)=O WQWMZOIPXWSZNE-WDSKDSINSA-N 0.000 description 1
YYOBUPFZLKQUAX-FXQIFTODSA-N Glu-Asn-Glu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O YYOBUPFZLKQUAX-FXQIFTODSA-N 0.000 description 1
101710183768 Glutamate carboxypeptidase 2 Proteins 0.000 description 1
ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 description 1
108010043121 Green Fluorescent Proteins Proteins 0.000 description 1
102000004144 Green Fluorescent Proteins Human genes 0.000 description 1
102100026122 High affinity immunoglobulin gamma Fc receptor I Human genes 0.000 description 1
101000690301 Homo sapiens Aldo-keto reductase family 1 member C4 Proteins 0.000 description 1
101000819490 Homo sapiens Alpha-(1,6)-fucosyltransferase Proteins 0.000 description 1
101100118549 Homo sapiens EGFR gene Proteins 0.000 description 1
101000920078 Homo sapiens Elongation factor 1-alpha 1 Proteins 0.000 description 1
101000851181 Homo sapiens Epidermal growth factor receptor Proteins 0.000 description 1
101000935587 Homo sapiens Flavin reductase (NADPH) Proteins 0.000 description 1
101100121078 Homo sapiens GAL gene Proteins 0.000 description 1
101000913074 Homo sapiens High affinity immunoglobulin gamma Fc receptor I Proteins 0.000 description 1
101001041117 Homo sapiens Hyaluronidase PH-20 Proteins 0.000 description 1
101000878602 Homo sapiens Immunoglobulin alpha Fc receptor Proteins 0.000 description 1
101000878605 Homo sapiens Low affinity immunoglobulin epsilon Fc receptor Proteins 0.000 description 1
101000917826 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor II-a Proteins 0.000 description 1
101000917824 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor II-b Proteins 0.000 description 1
101001023379 Homo sapiens Lysosome-associated membrane glycoprotein 1 Proteins 0.000 description 1
101001116548 Homo sapiens Protein CBFA2T1 Proteins 0.000 description 1
101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 1
102000003839 Human Proteins Human genes 0.000 description 1
108090000144 Human Proteins Proteins 0.000 description 1
108010003272 Hyaluronate lyase Proteins 0.000 description 1
102000001974 Hyaluronidases Human genes 0.000 description 1
IOVUXUSIGXCREV-DKIMLUQUSA-N Ile-Leu-Phe Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 IOVUXUSIGXCREV-DKIMLUQUSA-N 0.000 description 1
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical class C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
102000013463 Immunoglobulin Light Chains Human genes 0.000 description 1
108010065825 Immunoglobulin Light Chains Proteins 0.000 description 1
102100038005 Immunoglobulin alpha Fc receptor Human genes 0.000 description 1
238000012695 Interfacial polymerization Methods 0.000 description 1
102000008070 Interferon-gamma Human genes 0.000 description 1
108010074328 Interferon-gamma Proteins 0.000 description 1
108090001005 Interleukin-6 Proteins 0.000 description 1
102000004889 Interleukin-6 Human genes 0.000 description 1
108090001007 Interleukin-8 Proteins 0.000 description 1
102000004890 Interleukin-8 Human genes 0.000 description 1
101150008942 J gene Proteins 0.000 description 1
208000008839 Kidney Neoplasms Diseases 0.000 description 1
AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
QEFRNWWLZKMPFJ-ZXPFJRLXSA-N L-methionine (R)-S-oxide Chemical group C[S@@](=O)CC[C@H]([NH3+])C([O-])=O QEFRNWWLZKMPFJ-ZXPFJRLXSA-N 0.000 description 1
QEFRNWWLZKMPFJ-UHFFFAOYSA-N L-methionine sulphoxide Chemical group CS(=O)CCC(N)C(O)=O QEFRNWWLZKMPFJ-UHFFFAOYSA-N 0.000 description 1
FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
125000000174 L-prolyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(*)=O 0.000 description 1
125000000510 L-tryptophano group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C(C([H])([H])[C@@]([H])(C(O[H])=O)N([H])[*])C2=C1[H] 0.000 description 1
KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
102100038007 Low affinity immunoglobulin epsilon Fc receptor Human genes 0.000 description 1
102100029204 Low affinity immunoglobulin gamma Fc region receptor II-a Human genes 0.000 description 1
108060001084 Luciferase Proteins 0.000 description 1
239000005089 Luciferase Substances 0.000 description 1
208000028018 Lymphocytic leukaemia Diseases 0.000 description 1
206010025323 Lymphomas Diseases 0.000 description 1
102100035133 Lysosome-associated membrane glycoprotein 1 Human genes 0.000 description 1
239000004907 Macro-emulsion Substances 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
108091022912 Mannose-6-Phosphate Isomerase Proteins 0.000 description 1
206010027476 Metastases Diseases 0.000 description 1
101100261636 Methanothermobacter marburgensis (strain ATCC BAA-927 / DSM 2133 / JCM 14651 / NBRC 100331 / OCM 82 / Marburg) trpB2 gene Proteins 0.000 description 1
108020005196 Mitochondrial DNA Proteins 0.000 description 1
108010063954 Mucins Proteins 0.000 description 1
102000015728 Mucins Human genes 0.000 description 1
241000699660 Mus musculus Species 0.000 description 1
101100338482 Mus musculus Hcst gene Proteins 0.000 description 1
101100179075 Mus musculus Icos gene Proteins 0.000 description 1
101100404853 Mus musculus Klrk1 gene Proteins 0.000 description 1
101100427034 Mus musculus Tyrobp gene Proteins 0.000 description 1
JDHILDINMRGULE-LURJTMIESA-N N(pros)-methyl-L-histidine Chemical compound CN1C=NC=C1C[C@H](N)C(O)=O JDHILDINMRGULE-LURJTMIESA-N 0.000 description 1
NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 1
208000002454 Nasopharyngeal Carcinoma Diseases 0.000 description 1
206010061306 Nasopharyngeal cancer Diseases 0.000 description 1
229930193140 Neomycin Natural products 0.000 description 1
208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
241000238413 Octopus Species 0.000 description 1
108020005187 Oligonucleotide Probes Proteins 0.000 description 1
108010038807 Oligopeptides Proteins 0.000 description 1
102000015636 Oligopeptides Human genes 0.000 description 1
AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
229940122060 Ornithine decarboxylase inhibitor Drugs 0.000 description 1
240000007019 Oxalis corniculata Species 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
241000609499 Palicourea Species 0.000 description 1
108090000526 Papain Proteins 0.000 description 1
241001494479 Pecora Species 0.000 description 1
206010057249 Phagocytosis Diseases 0.000 description 1
JWBLQDDHSDGEGR-DRZSPHRISA-N Phe-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CC=CC=C1 JWBLQDDHSDGEGR-DRZSPHRISA-N 0.000 description 1
KIQUCMUULDXTAZ-HJOGWXRNSA-N Phe-Tyr-Tyr Chemical compound N[C@@H](Cc1ccccc1)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](Cc1ccc(O)cc1)C(O)=O KIQUCMUULDXTAZ-HJOGWXRNSA-N 0.000 description 1
AJFWREUFUPEYII-UHFFFAOYSA-N Phosphatidylserin Natural products CCCCCCCCCCCCCCCCCC(=O)OCC(COP(O)(=O)OCC([NH3+])C([O-])=O)OC(=O)CCCCCCCC=CCCCCCCCC AJFWREUFUPEYII-UHFFFAOYSA-N 0.000 description 1
102100035362 Phosphomannomutase 2 Human genes 0.000 description 1
101100124346 Photorhabdus laumondii subsp. laumondii (strain DSM 15139 / CIP 105565 / TT01) hisCD gene Proteins 0.000 description 1
206010060862 Prostate cancer Diseases 0.000 description 1
208000000236 Prostatic Neoplasms Diseases 0.000 description 1
102220480657 Protein LTV1 homolog_K53A_mutation Human genes 0.000 description 1
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
241000700157 Rattus norvegicus Species 0.000 description 1
101710100968 Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 1
101710100969 Receptor tyrosine-protein kinase erbB-3 Proteins 0.000 description 1
102100029986 Receptor tyrosine-protein kinase erbB-3 Human genes 0.000 description 1
102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
206010038389 Renal cancer Diseases 0.000 description 1
208000006265 Renal cell carcinoma Diseases 0.000 description 1
102000009661 Repressor Proteins Human genes 0.000 description 1
108010034634 Repressor Proteins Proteins 0.000 description 1
102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
241000714474 Rous sarcoma virus Species 0.000 description 1
101100123851 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) HER1 gene Proteins 0.000 description 1
206010039491 Sarcoma Diseases 0.000 description 1
238000012300 Sequence Analysis Methods 0.000 description 1
QMCDMHWAKMUGJE-IHRRRGAJSA-N Ser-Phe-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C(C)C)C(O)=O QMCDMHWAKMUGJE-IHRRRGAJSA-N 0.000 description 1
DKGRNFUXVTYRAS-UBHSHLNASA-N Ser-Ser-Trp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O DKGRNFUXVTYRAS-UBHSHLNASA-N 0.000 description 1
108010071390 Serum Albumin Proteins 0.000 description 1
102000007562 Serum Albumin Human genes 0.000 description 1
241000700584 Simplexvirus Species 0.000 description 1
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
241000256251 Spodoptera frugiperda Species 0.000 description 1
108091081024 Start codon Proteins 0.000 description 1
208000005718 Stomach Neoplasms Diseases 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
230000005867 T cell response Effects 0.000 description 1
108010092262 T-Cell Antigen Receptors Proteins 0.000 description 1
206010042971 T-cell lymphoma Diseases 0.000 description 1
208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 description 1
208000024313 Testicular Neoplasms Diseases 0.000 description 1
206010057644 Testis cancer Diseases 0.000 description 1
COYHRQWNJDJCNA-NUJDXYNKSA-N Thr-Thr-Thr Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O COYHRQWNJDJCNA-NUJDXYNKSA-N 0.000 description 1
208000024770 Thyroid neoplasm Diseases 0.000 description 1
108700019146 Transgenes Proteins 0.000 description 1
HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 1
108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
102100040247 Tumor necrosis factor Human genes 0.000 description 1
KHPLUFDSWGDRHD-SLFFLAALSA-N Tyr-Tyr-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CC=C(C=C2)O)NC(=O)[C@H](CC3=CC=C(C=C3)O)N)C(=O)O KHPLUFDSWGDRHD-SLFFLAALSA-N 0.000 description 1
101150117115 V gene Proteins 0.000 description 1
108050003842 V-set and immunoglobulin domain-containing protein 1 Proteins 0.000 description 1
241000700618 Vaccinia virus Species 0.000 description 1
206010000210 abortion Diseases 0.000 description 1
231100000176 abortion Toxicity 0.000 description 1
239000008351 acetate buffer Substances 0.000 description 1
230000021736 acetylation Effects 0.000 description 1
238000006640 acetylation reaction Methods 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
239000013543 active substance Substances 0.000 description 1
230000002730 additional effect Effects 0.000 description 1
229960000643 adenine Drugs 0.000 description 1
239000003463 adsorbent Substances 0.000 description 1
230000001270 agonistic effect Effects 0.000 description 1
238000003349 alamar blue assay Methods 0.000 description 1
125000000217 alkyl group Chemical group 0.000 description 1
HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
230000009435 amidation Effects 0.000 description 1
238000007112 amidation reaction Methods 0.000 description 1
150000003862 amino acid derivatives Chemical class 0.000 description 1
125000003277 amino group Chemical group 0.000 description 1
229940126575 aminoglycoside Drugs 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
210000004102 animal cell Anatomy 0.000 description 1
238000010171 animal model Methods 0.000 description 1
230000000340 anti-metabolite Effects 0.000 description 1
230000000692 anti-sense effect Effects 0.000 description 1
229940100197 antimetabolite Drugs 0.000 description 1
239000002256 antimetabolite Substances 0.000 description 1
239000003963 antioxidant agent Substances 0.000 description 1
235000006708 antioxidants Nutrition 0.000 description 1
230000006907 apoptotic process Effects 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
125000003118 aryl group Chemical group 0.000 description 1
229960005070 ascorbic acid Drugs 0.000 description 1
235000010323 ascorbic acid Nutrition 0.000 description 1
239000011668 ascorbic acid Substances 0.000 description 1
125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 1
230000001580 bacterial effect Effects 0.000 description 1
229960000686 benzalkonium chloride Drugs 0.000 description 1
229960001950 benzethonium chloride Drugs 0.000 description 1
UREZNYTWGJKWBI-UHFFFAOYSA-M benzethonium chloride Chemical compound [Cl-].C1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 UREZNYTWGJKWBI-UHFFFAOYSA-M 0.000 description 1
235000019445 benzyl alcohol Nutrition 0.000 description 1
CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
SQVRNKJHWKZAKO-UHFFFAOYSA-N beta-N-Acetyl-D-neuraminic acid Natural products CC(=O)NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO SQVRNKJHWKZAKO-UHFFFAOYSA-N 0.000 description 1
208000026900 bile duct neoplasm Diseases 0.000 description 1
238000013357 binding ELISA Methods 0.000 description 1
HUTDDBSSHVOYJR-UHFFFAOYSA-H bis[(2-oxo-1,3,2$l^{5},4$l^{2}-dioxaphosphaplumbetan-2-yl)oxy]lead Chemical compound [Pb+2].[Pb+2].[Pb+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O HUTDDBSSHVOYJR-UHFFFAOYSA-H 0.000 description 1
CXNPLSGKWMLZPZ-UHFFFAOYSA-N blasticidin-S Natural products O1C(C(O)=O)C(NC(=O)CC(N)CCN(C)C(N)=N)C=CC1N1C(=O)N=C(N)C=C1 CXNPLSGKWMLZPZ-UHFFFAOYSA-N 0.000 description 1
230000000903 blocking effect Effects 0.000 description 1
230000017531 blood circulation Effects 0.000 description 1
210000001185 bone marrow Anatomy 0.000 description 1
229940098773 bovine serum albumin Drugs 0.000 description 1
LRHPLDYGYMQRHN-UHFFFAOYSA-N butyl alcohol Substances CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
ZTQSAGDEMFDKMZ-UHFFFAOYSA-N butyric aldehyde Natural products CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 1
239000006227 byproduct Substances 0.000 description 1
239000001110 calcium chloride Substances 0.000 description 1
229910001628 calcium chloride Inorganic materials 0.000 description 1
238000005251 capillar electrophoresis Methods 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
239000001768 carboxy methyl cellulose Substances 0.000 description 1
235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
239000008112 carboxymethyl-cellulose Substances 0.000 description 1
239000006143 cell culture medium Substances 0.000 description 1
230000032823 cell division Effects 0.000 description 1
230000006037 cell lysis Effects 0.000 description 1
230000003833 cell viability Effects 0.000 description 1
230000036755 cellular response Effects 0.000 description 1
208000019065 cervical carcinoma Diseases 0.000 description 1
239000002738 chelating agent Substances 0.000 description 1
238000007385 chemical modification Methods 0.000 description 1
108700010039 chimeric receptor Proteins 0.000 description 1
230000001684 chronic effect Effects 0.000 description 1
239000013599 cloning vector Substances 0.000 description 1
238000009643 clonogenic assay Methods 0.000 description 1
231100000096 clonogenic assay Toxicity 0.000 description 1
238000003501 co-culture Methods 0.000 description 1
238000005354 coacervation Methods 0.000 description 1
208000029742 colonic neoplasm Diseases 0.000 description 1
238000004891 communication Methods 0.000 description 1
230000001447 compensatory effect Effects 0.000 description 1
238000012875 competitive assay Methods 0.000 description 1
230000024203 complement activation Effects 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
239000013078 crystal Substances 0.000 description 1
HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 1
230000016396 cytokine production Effects 0.000 description 1
229940104302 cytosine Drugs 0.000 description 1
210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
229940127089 cytotoxic agent Drugs 0.000 description 1
239000002254 cytotoxic agent Substances 0.000 description 1
231100000599 cytotoxic agent Toxicity 0.000 description 1
230000003013 cytotoxicity Effects 0.000 description 1
231100000135 cytotoxicity Toxicity 0.000 description 1
230000006378 damage Effects 0.000 description 1
230000002950 deficient Effects 0.000 description 1
230000001934 delay Effects 0.000 description 1
239000003405 delayed action preparation Substances 0.000 description 1
YSMODUONRAFBET-UHFFFAOYSA-N delta-DL-hydroxylysine Natural products NCC(O)CCC(N)C(O)=O YSMODUONRAFBET-UHFFFAOYSA-N 0.000 description 1
238000011161 development Methods 0.000 description 1
230000018109 developmental process Effects 0.000 description 1
229950006137 dexfosfoserine Drugs 0.000 description 1
235000019425 dextrin Nutrition 0.000 description 1
238000003745 diagnosis Methods 0.000 description 1
238000010586 diagram Methods 0.000 description 1
230000004069 differentiation Effects 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
238000000375 direct analysis in real time Methods 0.000 description 1
150000002016 disaccharides Chemical class 0.000 description 1
230000005750 disease progression Effects 0.000 description 1
239000006185 dispersion Substances 0.000 description 1
238000012377 drug delivery Methods 0.000 description 1
238000012063 dual-affinity re-targeting Methods 0.000 description 1
230000008030 elimination Effects 0.000 description 1
238000003379 elimination reaction Methods 0.000 description 1
229940066758 endopeptidases Drugs 0.000 description 1
YSMODUONRAFBET-UHNVWZDZSA-N erythro-5-hydroxy-L-lysine Chemical compound NC[C@H](O)CC[C@H](N)C(O)=O YSMODUONRAFBET-UHNVWZDZSA-N 0.000 description 1
201000004101 esophageal cancer Diseases 0.000 description 1
OGPBJKLSAFTDLK-UHFFFAOYSA-N europium atom Chemical compound [Eu] OGPBJKLSAFTDLK-UHFFFAOYSA-N 0.000 description 1
238000011156 evaluation Methods 0.000 description 1
230000005284 excitation Effects 0.000 description 1
210000001723 extracellular space Anatomy 0.000 description 1
210000003754 fetus Anatomy 0.000 description 1
238000001914 filtration Methods 0.000 description 1
238000007421 fluorometric assay Methods 0.000 description 1
230000005714 functional activity Effects 0.000 description 1
229930182830 galactose Natural products 0.000 description 1
206010017758 gastric cancer Diseases 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
210000004602 germ cell Anatomy 0.000 description 1
210000004907 gland Anatomy 0.000 description 1
239000011521 glass Substances 0.000 description 1
108060003196 globin Proteins 0.000 description 1
102000018146 globin Human genes 0.000 description 1
239000008103 glucose Substances 0.000 description 1
125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 1
ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
238000011194 good manufacturing practice Methods 0.000 description 1
239000001963 growth medium Substances 0.000 description 1
229940093915 gynecological organic acid Drugs 0.000 description 1
201000010536 head and neck cancer Diseases 0.000 description 1
208000014829 head and neck neoplasm Diseases 0.000 description 1
230000002489 hematologic effect Effects 0.000 description 1
210000003958 hematopoietic stem cell Anatomy 0.000 description 1
125000005842 heteroatom Chemical group 0.000 description 1
239000000833 heterodimer Substances 0.000 description 1
101150113423 hisD gene Proteins 0.000 description 1
102000045108 human EGFR Human genes 0.000 description 1
102000054751 human RUNX1T1 Human genes 0.000 description 1
102000049443 human SMCP Human genes 0.000 description 1
210000005260 human cell Anatomy 0.000 description 1
229960002773 hyaluronidase Drugs 0.000 description 1
229910052739 hydrogen Inorganic materials 0.000 description 1
150000002431 hydrogen Chemical group 0.000 description 1
239000001257 hydrogen Substances 0.000 description 1
229920001477 hydrophilic polymer Polymers 0.000 description 1
230000002209 hydrophobic effect Effects 0.000 description 1
229920001600 hydrophobic polymer Polymers 0.000 description 1
WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
229940044700 hylenex Drugs 0.000 description 1
239000012642 immune effector Substances 0.000 description 1
230000008076 immune mechanism Effects 0.000 description 1
238000002649 immunization Methods 0.000 description 1
229940121354 immunomodulator Drugs 0.000 description 1
230000001024 immunotherapeutic effect Effects 0.000 description 1
238000010348 incorporation Methods 0.000 description 1
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
230000036512 infertility Effects 0.000 description 1
230000004941 influx Effects 0.000 description 1
210000004964 innate lymphoid cell Anatomy 0.000 description 1
229960003130 interferon gamma Drugs 0.000 description 1
238000001361 intraarterial administration Methods 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000007912 intraperitoneal administration Methods 0.000 description 1
238000010253 intravenous injection Methods 0.000 description 1
238000004255 ion exchange chromatography Methods 0.000 description 1
238000005304 joining Methods 0.000 description 1
229960000318 kanamycin Drugs 0.000 description 1
SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 1
229930027917 kanamycin Natural products 0.000 description 1
229930182823 kanamycin A Natural products 0.000 description 1
201000010982 kidney cancer Diseases 0.000 description 1
238000011005 laboratory method Methods 0.000 description 1
125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
208000032839 leukemia Diseases 0.000 description 1
239000003446 ligand Substances 0.000 description 1
238000011068 loading method Methods 0.000 description 1
210000005265 lung cell Anatomy 0.000 description 1
238000002824 mRNA display Methods 0.000 description 1
229920002521 macromolecule Polymers 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
230000008774 maternal effect Effects 0.000 description 1
239000011159 matrix material Substances 0.000 description 1
238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 1
210000002901 mesenchymal stem cell Anatomy 0.000 description 1
230000009401 metastasis Effects 0.000 description 1
229960000485 methotrexate Drugs 0.000 description 1
239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
229960002216 methylparaben Drugs 0.000 description 1
LSDPWZHWYPCBBB-UHFFFAOYSA-O methylsulfide anion Chemical compound [SH2+]C LSDPWZHWYPCBBB-UHFFFAOYSA-O 0.000 description 1
239000004530 micro-emulsion Substances 0.000 description 1
238000000386 microscopy Methods 0.000 description 1
239000004005 microsphere Substances 0.000 description 1
230000002438 mitochondrial effect Effects 0.000 description 1
238000002156 mixing Methods 0.000 description 1
108091005601 modified peptides Proteins 0.000 description 1
239000003607 modifier Substances 0.000 description 1
238000009126 molecular therapy Methods 0.000 description 1
238000012544 monitoring process Methods 0.000 description 1
239000000178 monomer Substances 0.000 description 1
150000002772 monosaccharides Chemical class 0.000 description 1
210000000066 myeloid cell Anatomy 0.000 description 1
208000025113 myeloid leukemia Diseases 0.000 description 1
229950006780 n-acetylglucosamine Drugs 0.000 description 1
239000002088 nanocapsule Substances 0.000 description 1
239000002105 nanoparticle Substances 0.000 description 1
201000011216 nasopharynx carcinoma Diseases 0.000 description 1
229960004927 neomycin Drugs 0.000 description 1
108010068617 neonatal Fc receptor Proteins 0.000 description 1
210000000440 neutrophil Anatomy 0.000 description 1
239000002736 nonionic surfactant Substances 0.000 description 1
239000002751 oligonucleotide probe Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
229960003104 ornithine Drugs 0.000 description 1
239000002818 ornithine decarboxylase inhibitor Substances 0.000 description 1
201000008968 osteosarcoma Diseases 0.000 description 1
LXCFILQKKLGQFO-UHFFFAOYSA-N p-hydroxybenzoic acid methyl ester Natural products COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
229940055729 papain Drugs 0.000 description 1
235000019834 papain Nutrition 0.000 description 1
230000008506 pathogenesis Effects 0.000 description 1
230000001575 pathological effect Effects 0.000 description 1
230000007170 pathology Effects 0.000 description 1
230000037361 pathway Effects 0.000 description 1
210000005259 peripheral blood Anatomy 0.000 description 1
239000011886 peripheral blood Substances 0.000 description 1
210000001322 periplasm Anatomy 0.000 description 1
229960002087 pertuzumab Drugs 0.000 description 1
230000008782 phagocytosis Effects 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
230000026731 phosphorylation Effects 0.000 description 1
238000006366 phosphorylation reaction Methods 0.000 description 1
239000013600 plasmid vector Substances 0.000 description 1
229920003023 plastic Polymers 0.000 description 1
239000004033 plastic Substances 0.000 description 1
210000002706 plastid Anatomy 0.000 description 1
229920000191 poly(N-vinyl pyrrolidone) Polymers 0.000 description 1
229920001308 poly(aminoacid) Polymers 0.000 description 1
229920001583 poly(oxyethylated polyols) Polymers 0.000 description 1
108010054442 polyalanine Proteins 0.000 description 1
230000001323 posttranslational effect Effects 0.000 description 1
239000001608 potassium adipate Substances 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
230000002335 preservative effect Effects 0.000 description 1
230000003449 preventive effect Effects 0.000 description 1
239000013615 primer Substances 0.000 description 1
230000008569 process Effects 0.000 description 1
238000012545 processing Methods 0.000 description 1
229940002612 prodrug Drugs 0.000 description 1
239000000651 prodrug Substances 0.000 description 1
238000004393 prognosis Methods 0.000 description 1
230000001902 propagating effect Effects 0.000 description 1
238000011321 prophylaxis Methods 0.000 description 1
XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 1
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
229960003415 propylparaben Drugs 0.000 description 1
235000019419 proteases Nutrition 0.000 description 1
108020001775 protein parts Proteins 0.000 description 1
230000004850 protein–protein interaction Effects 0.000 description 1
230000002797 proteolythic effect Effects 0.000 description 1
230000006337 proteolytic cleavage Effects 0.000 description 1
229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 1
238000010791 quenching Methods 0.000 description 1
230000000171 quenching effect Effects 0.000 description 1
238000007420 radioactive assay Methods 0.000 description 1
229920005604 random copolymer Polymers 0.000 description 1
230000008707 rearrangement Effects 0.000 description 1
230000007115 recruitment Effects 0.000 description 1
208000037922 refractory disease Diseases 0.000 description 1
208000015347 renal cell adenocarcinoma Diseases 0.000 description 1
231100000205 reproductive and developmental toxicity Toxicity 0.000 description 1
238000004007 reversed phase HPLC Methods 0.000 description 1
TUFFYSFVSYUHPA-UHFFFAOYSA-M rhodamine 123 Chemical compound [Cl-].COC(=O)C1=CC=CC=C1C1=C(C=CC(N)=C2)C2=[O+]C2=C1C=CC(N)=C2 TUFFYSFVSYUHPA-UHFFFAOYSA-M 0.000 description 1
210000003705 ribosome Anatomy 0.000 description 1
101150049069 rpsM gene Proteins 0.000 description 1
238000009781 safety test method Methods 0.000 description 1
230000003248 secreting effect Effects 0.000 description 1
230000035945 sensitivity Effects 0.000 description 1
210000000717 sertoli cell Anatomy 0.000 description 1
SQVRNKJHWKZAKO-OQPLDHBCSA-N sialic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)OC1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-OQPLDHBCSA-N 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011734 sodium Substances 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
239000001601 sodium adipate Substances 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
JUJBNYBVVQSIOU-UHFFFAOYSA-M sodium;4-[2-(4-iodophenyl)-3-(4-nitrophenyl)tetrazol-2-ium-5-yl]benzene-1,3-disulfonate Chemical compound [Na+].C1=CC([N+](=O)[O-])=CC=C1N1[N+](C=2C=CC(I)=CC=2)=NC(C=2C(=CC(=CC=2)S([O-])(=O)=O)S([O-])(=O)=O)=N1 JUJBNYBVVQSIOU-UHFFFAOYSA-M 0.000 description 1
JACYMBNQPPWQML-UHFFFAOYSA-N sodium;4-methoxy-5-[3-(2-methoxy-4-nitro-5-sulfophenyl)-5-(phenylcarbamoyl)tetrazol-3-ium-2-yl]-2-nitrobenzenesulfonate Chemical compound [Na+].COC1=CC([N+]([O-])=O)=C(S([O-])(=O)=O)C=C1N1[N+](C=2C(=CC(=C(C=2)S(O)(=O)=O)[N+]([O-])=O)OC)=NC(C(=O)NC=2C=CC=CC=2)=N1 JACYMBNQPPWQML-UHFFFAOYSA-N 0.000 description 1
239000007787 solid Substances 0.000 description 1
230000000392 somatic effect Effects 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
230000000087 stabilizing effect Effects 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
SFVFIFLLYFPGHH-UHFFFAOYSA-M stearalkonium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 SFVFIFLLYFPGHH-UHFFFAOYSA-M 0.000 description 1
210000000130 stem cell Anatomy 0.000 description 1
238000011146 sterile filtration Methods 0.000 description 1
150000003431 steroids Chemical class 0.000 description 1
201000011549 stomach cancer Diseases 0.000 description 1
238000003860 storage Methods 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
238000010254 subcutaneous injection Methods 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
230000001629 suppression Effects 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
239000000725 suspension Substances 0.000 description 1
230000002459 sustained effect Effects 0.000 description 1
238000013268 sustained release Methods 0.000 description 1
239000012730 sustained-release form Substances 0.000 description 1
230000002123 temporal effect Effects 0.000 description 1
201000003120 testicular cancer Diseases 0.000 description 1
238000012360 testing method Methods 0.000 description 1
229940126622 therapeutic monoclonal antibody Drugs 0.000 description 1
125000003396 thiol group Chemical group [H]S* 0.000 description 1
229940113082 thymine Drugs 0.000 description 1
210000001685 thyroid gland Anatomy 0.000 description 1
238000004448 titration Methods 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
231100000041 toxicology testing Toxicity 0.000 description 1
FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 1
230000005030 transcription termination Effects 0.000 description 1
239000012096 transfection reagent Substances 0.000 description 1
230000001131 transforming effect Effects 0.000 description 1
238000011830 transgenic mouse model Methods 0.000 description 1
230000014621 translational initiation Effects 0.000 description 1
102000035160 transmembrane proteins Human genes 0.000 description 1
108091005703 transmembrane proteins Proteins 0.000 description 1
101150081616 trpB gene Proteins 0.000 description 1
101150111232 trpB-1 gene Proteins 0.000 description 1
125000000430 tryptophan group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
241001529453 unidentified herpesvirus Species 0.000 description 1
241001430294 unidentified retrovirus Species 0.000 description 1
230000003827 upregulation Effects 0.000 description 1
238000011144 upstream manufacturing Methods 0.000 description 1
229940035893 uracil Drugs 0.000 description 1
229960005486 vaccine Drugs 0.000 description 1
239000004474 valine Substances 0.000 description 1
125000002987 valine group Chemical group [H]N([H])C([H])(C(*)=O)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
230000035899 viability Effects 0.000 description 1
230000003612 virological effect Effects 0.000 description 1
238000013389 whole blood assay Methods 0.000 description 1
210000005253 yeast cell Anatomy 0.000 description 1

Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/40—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/461—Cellular immunotherapy characterised by the cell type used
- A61K39/4611—T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/463—Cellular immunotherapy characterised by recombinant expression
- A61K39/4631—Chimeric Antigen Receptors [CAR]
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/7051—T-cell receptor (TcR)-CD3 complex
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2887—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against CD20
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
- C07K16/3007—Carcino-embryonic Antigens
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/42—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against immunoglobulins
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0634—Cells from the blood or the immune system
- C12N5/0636—T lymphocytes
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/40—Immunoglobulins specific features characterized by post-translational modification
- C07K2317/41—Glycosylation, sialylation, or fucosylation
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
- C07K2317/524—CH2 domain
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/55—Fab or Fab'
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/622—Single chain antibody (scFv)
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/71—Decreased effector function due to an Fc-modification
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K2317/732—Antibody-dependent cellular cytotoxicity [ADCC]
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/03—Fusion polypeptide containing a localisation/targetting motif containing a transmembrane segment
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2510/00—Genetically modified cells

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Immunology (AREA)
Organic Chemistry (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Genetics & Genomics (AREA)
Biochemistry (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Molecular Biology (AREA)
Biophysics (AREA)
Cell Biology (AREA)
Engineering & Computer Science (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Pharmacology & Pharmacy (AREA)
Veterinary Medicine (AREA)
Zoology (AREA)
Biomedical Technology (AREA)
Microbiology (AREA)
Biotechnology (AREA)
Bioinformatics & Cheminformatics (AREA)
Wood Science & Technology (AREA)
Epidemiology (AREA)
Mycology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Oncology (AREA)
Hematology (AREA)
Toxicology (AREA)
Gastroenterology & Hepatology (AREA)
General Engineering & Computer Science (AREA)
Peptides Or Proteins (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Micro-Organisms Or Cultivation Processes Thereof (AREA)

CA3219606A 2021-07-22 2022-07-20 Heterodimeric fc domain antibodies Pending CA3219606A1 (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
EP21187191.8		2021-07-22
EP21187191		2021-07-22
PCT/EP2022/070338 WO2023001884A1 (en)	2021-07-22	2022-07-20	Heterodimeric fc domain antibodies

Publications (1)

Publication Number	Publication Date
CA3219606A1 true CA3219606A1 (en)	2023-01-26

Family

ID=77021264

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA3219606A Pending CA3219606A1 (en)	2021-07-22	2022-07-20	Heterodimeric fc domain antibodies

Country Status (8)

Country	Link
EP (1)	EP4373859A1 (zh)
KR (1)	KR20240036570A (zh)
CN (1)	CN117730102A (zh)
AR (1)	AR126556A1 (zh)
AU (1)	AU2022315528A1 (zh)
CA (1)	CA3219606A1 (zh)
TW (1)	TW202323294A (zh)
WO (1)	WO2023001884A1 (zh)

Family Cites Families (108)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4676980A (en)	1985-09-23	1987-06-30	The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services	Target specific cross-linked heteroantibodies
US6548640B1 (en)	1986-03-27	2003-04-15	Btg International Limited	Altered antibodies
IL85035A0 (en)	1987-01-08	1988-06-30	Int Genetic Eng	Polynucleotide molecule,a chimeric antibody with specificity for human b cell surface antigen,a process for the preparation and methods utilizing the same
JP3101690B2 (ja)	1987-03-18	2000-10-23	エス・ビィ・２・インコーポレイテッド	変性抗体の、または変性抗体に関する改良
JP2919890B2 (ja)	1988-11-11	1999-07-19	メディカルリサーチカウンスル	単一ドメインリガンド、そのリガンドからなる受容体、その製造方法、ならびにそのリガンドおよび受容体の使用
US5703055A (en)	1989-03-21	1997-12-30	Wisconsin Alumni Research Foundation	Generation of antibodies through lipid mediated DNA delivery
US5959177A (en)	1989-10-27	1999-09-28	The Scripps Research Institute	Transgenic plants expressing assembled secretory antibodies
US6150584A (en)	1990-01-12	2000-11-21	Abgenix, Inc.	Human antibodies derived from immunized xenomice
US6075181A (en)	1990-01-12	2000-06-13	Abgenix, Inc.	Human antibodies derived from immunized xenomice
US5770429A (en)	1990-08-29	1998-06-23	Genpharm International, Inc.	Transgenic non-human animals capable of producing heterologous antibodies
DK0564531T3 (da)	1990-12-03	1998-09-28	Genentech Inc	Berigelsesfremgangsmåde for variantproteiner med ændrede bindingsegenskaber
US5571894A (en)	1991-02-05	1996-11-05	Ciba-Geigy Corporation	Recombinant antibodies specific for a growth factor receptor
CA2103059C (en)	1991-06-14	2005-03-22	Paul J. Carter	Method for making humanized antibodies
GB9304200D0 (en)	1993-03-02	1993-04-21	Sandoz Ltd	Improvements in or relating to organic compounds
WO1993006217A1 (en)	1991-09-19	1993-04-01	Genentech, Inc.	EXPRESSION IN E. COLI OF ANTIBODY FRAGMENTS HAVING AT LEAST A CYSTEINE PRESENT AS A FREE THIOL, USE FOR THE PRODUCTION OF BIFUNCTIONAL F(ab')2 ANTIBODIES
US5587458A (en)	1991-10-07	1996-12-24	Aronex Pharmaceuticals, Inc.	Anti-erbB-2 antibodies, combinations thereof, and therapeutic and diagnostic uses thereof
EP0625200B1 (en)	1992-02-06	2005-05-11	Chiron Corporation	Biosynthetic binding protein for cancer marker
JP3626187B2 (ja)	1993-06-07	2005-03-02	バイカルインコーポレイテッド	遺伝子治療に適するプラスミド
WO1994029351A2 (en)	1993-06-16	1994-12-22	Celltech Limited	Antibodies
US5789199A (en)	1994-11-03	1998-08-04	Genentech, Inc.	Process for bacterial production of polypeptides
US5731168A (en)	1995-03-01	1998-03-24	Genentech, Inc.	Method for making heteromultimeric polypeptides
US5840523A (en)	1995-03-01	1998-11-24	Genetech, Inc.	Methods and compositions for secretion of heterologous polypeptides
WO1997000957A1 (en)	1995-06-23	1997-01-09	President And Fellows Of Harvard College	Transcriptional regulation of genes encoding vascular endothelial growth factor receptors
US6267958B1 (en)	1995-07-27	2001-07-31	Genentech, Inc.	Protein formulation
GB9603256D0 (en)	1996-02-16	1996-04-17	Wellcome Found	Antibodies
WO1998050431A2 (en)	1997-05-02	1998-11-12	Genentech, Inc.	A method for making multispecific antibodies having heteromultimeric and common components
US6171586B1 (en)	1997-06-13	2001-01-09	Genentech, Inc.	Antibody formulation
PT994903E (pt)	1997-06-24	2005-10-31	Genentech Inc	Metodos e composicoes para glicoproteinas galactosiladas
US6040498A (en)	1998-08-11	2000-03-21	North Caroline State University	Genetically engineered duckweed
WO1999022764A1 (en)	1997-10-31	1999-05-14	Genentech, Inc.	Methods and compositions comprising glycoprotein glycoforms
US6610833B1 (en)	1997-11-24	2003-08-26	The Institute For Human Genetics And Biochemistry	Monoclonal human natural antibodies
WO1999029888A1 (en)	1997-12-05	1999-06-17	The Scripps Research Institute	Humanization of murine antibody
US6194551B1 (en)	1998-04-02	2001-02-27	Genentech, Inc.	Polypeptide variants
PT1068241E (pt)	1998-04-02	2007-11-19	Genentech Inc	Variantes de anticorpos e respectivos fragmentos
DK2180007T4 (da)	1998-04-20	2017-11-27	Roche Glycart Ag	Glycosyleringsteknik for antistoffer til forbedring af antistofafhængig cellecytotoxicitet
US6737056B1 (en)	1999-01-15	2004-05-18	Genentech, Inc.	Polypeptide variants with altered effector function
MXPA01007170A (es)	1999-01-15	2002-07-30	Genentech Inc	Variantes de polipeptidos con funcion efectora alterada.
EP1196570A2 (en)	1999-07-26	2002-04-17	Genentech, Inc.	Human polypeptides and methods for the use thereof
BR0014480A (pt)	1999-10-04	2002-06-11	Medicago Inc	Método para regular a transcrição de genes estranhos
US7125978B1 (en)	1999-10-04	2006-10-24	Medicago Inc.	Promoter for regulating expression of foreign genes
JP2003516755A (ja)	1999-12-15	2003-05-20	ジェネンテック・インコーポレーテッド	ショットガン走査、すなわち機能性タンパク質エピトープをマッピングするための組み合わせ方法
SI2857516T1 (sl)	2000-04-11	2017-09-29	Genentech, Inc.	Multivalentna protitelesa in njihove uporabe
US6596541B2 (en)	2000-10-31	2003-07-22	Regeneron Pharmaceuticals, Inc.	Methods of modifying eukaryotic cells
ES2295228T3 (es)	2000-11-30	2008-04-16	Medarex, Inc.	Roedores transcromosomicos transgenicos para la preparacion de anticuerpos humanos.
MXPA04001072A (es)	2001-08-03	2005-02-17	Glycart Biotechnology Ag	Variantes de glicosilacion de anticuerpos que tienen citotoxicidad celulares dependiente de anticuerpos incrementada.
BR0213761A (pt)	2001-10-25	2005-04-12	Genentech Inc	Composições, preparação farmacêutica, artigo industrializado, método de tratamento de mamìferos, célula hospedeira, método para a produção de uma glicoproteìna e uso da composição
US20040093621A1 (en)	2001-12-25	2004-05-13	Kyowa Hakko Kogyo Co., Ltd	Antibody composition which specifically binds to CD20
ATE503829T1 (de)	2002-04-09	2011-04-15	Kyowa Hakko Kirin Co Ltd	Zelle mit erniedrigter oder deletierter aktivität eines am gdp-fucosetransport beteiligten proteins
AU2003236019A1 (en)	2002-04-09	2003-10-20	Kyowa Hakko Kirin Co., Ltd.	Drug containing antibody composition appropriate for patient suffering from Fc Gamma RIIIa polymorphism
CA2481837A1 (en)	2002-04-09	2003-10-16	Kyowa Hakko Kogyo Co., Ltd.	Production process for antibody composition
WO2003085119A1 (fr)	2002-04-09	2003-10-16	Kyowa Hakko Kogyo Co., Ltd.	Procede d'amelioration de l'activite d'une composition d'anticorps de liaison avec le recepteur fc$g(g) iiia
WO2003085107A1 (fr)	2002-04-09	2003-10-16	Kyowa Hakko Kogyo Co., Ltd.	Cellules à génome modifié
EP1513879B1 (en)	2002-06-03	2018-08-22	Genentech, Inc.	Synthetic antibody phage libraries
US7361740B2 (en)	2002-10-15	2008-04-22	Pdl Biopharma, Inc.	Alteration of FcRn binding affinities or serum half-lives of antibodies by mutagenesis
RS51318B (sr)	2002-12-16	2010-12-31	Genentech Inc.	Varijante imunoglobulina i njihova upotreba
CA2510003A1 (en)	2003-01-16	2004-08-05	Genentech, Inc.	Synthetic antibody phage libraries
ATE475708T1 (de)	2003-01-22	2010-08-15	Glycart Biotechnology Ag	Fusionskonstrukte und deren verwendung zur produktion von antikörpern mit erhöhter fc rezeptor bindungsaffinität und effektorfunktion
US20060104968A1 (en)	2003-03-05	2006-05-18	Halozyme, Inc.	Soluble glycosaminoglycanases and methods of preparing and using soluble glycosaminogly ycanases
US7871607B2 (en)	2003-03-05	2011-01-18	Halozyme, Inc.	Soluble glycosaminoglycanases and methods of preparing and using soluble glycosaminoglycanases
JP2008501621A (ja)	2003-05-31	2008-01-24	マイクロメットアクツィエンゲゼルシャフト	Ｂ細胞関連疾患を処置するための二重特異性抗ｃｄ３、抗ｃｄ１９抗体構築物を含む薬学的組成物
US7235641B2 (en)	2003-12-22	2007-06-26	Micromet Ag	Bispecific antibodies
NZ550217A (en)	2004-03-31	2009-11-27	Genentech Inc	Humanized anti-TGF-beta antibodies
US7785903B2 (en)	2004-04-09	2010-08-31	Genentech, Inc.	Variable domain library and uses
EP2374817B1 (en)	2004-04-13	2017-09-06	F. Hoffmann-La Roche AG	Anti-P-selectin antibodies
TWI309240B (en)	2004-09-17	2009-05-01	Hoffmann La Roche	Anti-ox40l antibodies
AU2005286607B2 (en)	2004-09-23	2011-01-27	Genentech, Inc.	Cysteine engineered antibodies and conjugates
JO3000B1 (ar)	2004-10-20	2016-09-05	Genentech Inc	مركبات أجسام مضادة .
KR101569300B1 (ko)	2005-02-07	2015-11-13	로슈 글리카트 아게	Ｅｇｆｒ 에 결합하는 항원 결합 분자, 이를 코딩하는 벡터, 및 그의 용도
WO2006106905A1 (ja)	2005-03-31	2006-10-12	Chugai Seiyaku Kabushiki Kaisha	会合制御によるポリペプチド製造方法
AU2006301492B2 (en)	2005-10-11	2011-06-09	Amgen Research (Munich) Gmbh	Compositions comprising cross-species-specific antibodies and uses thereof
US20070237764A1 (en)	2005-12-02	2007-10-11	Genentech, Inc.	Binding polypeptides with restricted diversity sequences
ES2395969T3 (es)	2006-03-24	2013-02-18	Merck Patent Gmbh	Dominios de proteínas heterodiméricas genéticamente modificados
EP2016101A2 (en)	2006-05-09	2009-01-21	Genentech, Inc.	Binding polypeptides with optimized scaffolds
JP2009541275A (ja)	2006-06-22	2009-11-26	ノボ・ノルデイスク・エー／エス	二重特異性抗体の生産
US20080044455A1 (en)	2006-08-21	2008-02-21	Chaim Welczer	Tonsillitus Treatment
WO2008027236A2 (en)	2006-08-30	2008-03-06	Genentech, Inc.	Multispecific antibodies
DE102007001370A1 (de)	2007-01-09	2008-07-10	Curevac Gmbh	RNA-kodierte Antikörper
WO2008119567A2 (en)	2007-04-03	2008-10-09	Micromet Ag	Cross-species-specific cd3-epsilon binding domain
US20090162359A1 (en)	2007-12-21	2009-06-25	Christian Klein	Bivalent, bispecific antibodies
US8242247B2 (en)	2007-12-21	2012-08-14	Hoffmann-La Roche Inc.	Bivalent, bispecific antibodies
US9266967B2 (en)	2007-12-21	2016-02-23	Hoffmann-La Roche, Inc.	Bivalent, bispecific antibodies
PT2235064E (pt)	2008-01-07	2016-03-01	Amgen Inc	Método de preparação de moléculas heterodiméricas de fc de anticorpos utilizando efeitos de indução eletrostática
CA2756244A1 (en)	2009-04-02	2010-10-07	Roche Glycart Ag	Multispecific antibodies comprising full length antibodies and single chain fab fragments
EP2417156B1 (en)	2009-04-07	2015-02-11	Roche Glycart AG	Trivalent, bispecific antibodies
WO2010129304A2 (en)	2009-04-27	2010-11-11	Oncomed Pharmaceuticals, Inc.	Method for making heteromultimeric molecules
CN102448985B (zh)	2009-05-27	2015-08-05	霍夫曼-拉罗奇有限公司	三或四特异性抗体
US9676845B2 (en)	2009-06-16	2017-06-13	Hoffmann-La Roche, Inc.	Bispecific antigen binding proteins
CN104945509A (zh)	2009-09-16	2015-09-30	弗·哈夫曼-拉罗切有限公司	包含卷曲螺旋和/或系链的蛋白质复合体及其用途
EP3112382A1 (en)	2009-12-29	2017-01-04	Emergent Product Development Seattle, LLC	Heterodimer binding proteins and uses thereof
JP6022444B2 (ja)	2010-05-14	2016-11-09	ライナットニューロサイエンスコーポレイション	ヘテロ二量体タンパク質ならびにそれを生産および精製するための方法
CN114246952A (zh)	2010-06-08	2022-03-29	基因泰克公司	半胱氨酸改造的抗体和偶联物
JP6167040B2 (ja)	2010-11-05	2017-07-19	ザイムワークス，インコーポレイテッド	Ｆｃドメイン中に突然変異を有する、安定したヘテロ二量体抗体の設計
SG193554A1 (en)	2011-03-29	2013-11-29	Roche Glycart Ag	Antibody fc variants
PL2748202T3 (pl)	2011-08-23	2018-12-31	Roche Glycart Ag	Dwuswoiste cząsteczki wiążące antygen
LT2748201T (lt)	2011-08-23	2018-02-26	Roche Glycart Ag	Dvigubai specifinė t ląsteles aktyvinantį antigeną surišanti molekulė
CN107586340B (zh)	2011-08-23	2022-01-21	罗切格利卡特公司	对t细胞活化性抗原和肿瘤抗原特异性的双特异性抗体及使用方法
WO2013096291A2 (en)	2011-12-20	2013-06-27	Medimmune, Llc	Modified polypeptides for bispecific antibody scaffolds
JP6152120B2 (ja)	2012-02-15	2017-06-21	エフ．ホフマン−ラロシュアーゲーＦ．Ｈｏｆｆｍａｎｎ−ＬａＲｏｃｈｅＡｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ	Ｆｃ受容体に基づくアフィニティークロマトグラフィー
PT2838918T (pt)	2012-04-20	2019-08-23	Merus Nv	Métodos e meios para a produção de moléculas heterrodiméricas do tipo ig
MX2016006529A (es)	2013-12-20	2016-08-03	Genentech Inc	Anticuerpos dobles especificos.
UA117289C2 (uk)	2014-04-02	2018-07-10	Ф. Хоффманн-Ля Рош Аг	Мультиспецифічне антитіло
WO2016016299A1 (en)	2014-07-29	2016-02-04	F. Hoffmann-La Roche Ag	Multispecific antibodies
DK3177643T3 (da)	2014-08-04	2019-07-15	Hoffmann La Roche	Bispecifikke T-celle-aktiverende antigenbindende molekyler
BR112017003236A2 (pt)	2014-09-12	2017-11-28	Genentech Inc	anticorpos elaborados com cisteína, conjugados de droga e anticorpos, método de preparação de conjugado de droga e anticorpo e composição farmacêutica
JP6952605B2 (ja)	2015-04-24	2021-10-20	ジェネンテック，インコーポレイテッド	多特異性抗原結合タンパク質
CR20190440A (es)	2017-03-27	2019-11-12	Hoffmann La Roche	Receptores de unión a antígeno mejorados
US20220119533A1 (en) *	2018-10-23	2022-04-21	Dragonfly Therapeutics, Inc.	Heterodimeric fc-fused proteins
JP2023547447A (ja) *	2020-10-28	2023-11-10	エフ・ホフマン－ラ・ロシュ・アクチェンゲゼルシャフト	改良型抗原結合受容体

2022
- 2022-07-20 KR KR1020247002046A patent/KR20240036570A/ko unknown
- 2022-07-20 EP EP22754381.6A patent/EP4373859A1/en active Pending
- 2022-07-20 WO PCT/EP2022/070338 patent/WO2023001884A1/en active Application Filing
- 2022-07-20 CN CN202280050473.5A patent/CN117730102A/zh active Pending
- 2022-07-20 CA CA3219606A patent/CA3219606A1/en active Pending
- 2022-07-20 AU AU2022315528A patent/AU2022315528A1/en active Pending
- 2022-07-21 TW TW111127383A patent/TW202323294A/zh unknown
- 2022-07-22 AR ARP220101957A patent/AR126556A1/es unknown

Also Published As

Publication number	Publication date
AR126556A1 (es)	2023-10-18
KR20240036570A (ko)	2024-03-20
CN117730102A (zh)	2024-03-19
EP4373859A1 (en)	2024-05-29
AU2022315528A1 (en)	2023-10-19
TW202323294A (zh)	2023-06-16
WO2023001884A1 (en)	2023-01-26

Publication	Publication Date	Title
US11613587B2 (en)	2023-03-28	Combination therapy of T cell activating bispecific antigen binding molecules and PD-1 axis binding antagonists
US11524991B2 (en)	2022-12-13	PD-1 targeted heterodimeric fusion proteins containing IL-15/IL-15Ra Fc-fusion proteins and PD-1 antigen binding domains and uses thereof
CA3123493A1 (en)	2020-06-25	Tumor-targeted agonistic cd28 antigen binding molecules
CA3056837A1 (en)	2018-10-04	Improved antigen binding receptors
CA2929256A1 (en)	2015-05-07	Production of t cell retargeting hetero-dimeric immunoglobulins
WO2020027330A1 (ja)	2020-02-06	互いに連結された２つの抗原結合ドメインを含む抗原結合分子
EP4126946A1 (en)	2023-02-08	Bispecific antibodies comprising a modified c-terminal crossfab fragment
US20230357431A1 (en)	2023-11-09	Improved antigen binding receptors
CA3176579A1 (en)	2021-12-23	Antibodies binding to cd3
US20230322950A1 (en)	2023-10-12	Antigen binding receptors
CN117480185A (zh)	2024-01-30	靶向EpCAM的激动性CD28抗原结合分子
CA3199839A1 (en)	2022-05-12	Anti-cd19 agent and b cell targeting agent combination therapy for treating b cell malignancies
CA3219606A1 (en)	2023-01-26	Heterodimeric fc domain antibodies
CA3237616A1 (en)	2023-06-01	Improved antigen binding receptors
WO2024100170A1 (en)	2024-05-16	Antibodies binding to hla-a*02/foxp3